Method of making 6,10,14-trimethylpentadecanone-2



Patented Nov. 21, 1944 METHOD OF MAKING BJQJL-TBIIKETHYL- PENTADEOANONE-B Lee Irvin Smith and Joseph A. Sprung, Minneapolis, Ilium, assis'nors versity of Minnesota. Minneapolis, Minn., a corporation 0! Minnesota No Drawing. Application August 1, 1942 Serlal No, 453,280

3 Claims. ((11.269-593) This invention relates to new methods 01' makins 640,14-trimethyl-pentadecanone-2 which is useful in the preparation or phytol, iso hvtol and phytoi and isophytol derivatives.

The preparation of 6,10,14-trimethyl-pentadecanone-z has heretofore been accomplished by utilizing natural phytol, an expensive material, and while synthues have been provided, Annalee 464, 69 (1928) 476, 183 (1929), Helvetica Chimica Acta, 32, 610 (1939).- they have not completely satisfied requirements because oi the complex procedures, and the low yields involved.

It is an obiect or the present invention to provide an improved method of synthuizing 6,10,14- trimethyl-pentadecsnone-2 utilizing available, relatively inexpensive ingredients and involving emcient procedural steps.

In carrying out the invention there is utilized, as one starting ingredient. a Grisnard reagent. 4,8,12 trimethyl tridecyl magnesium halide which may be prepared from masnesium and i-halo-4,8,12-trimethyl -tridecane. The latter may be prepared conveniently in several steps and at low cost, from peeudoionone, as described in moo-pending application Ber. No. 453,281, iiled August 1, i942. and as described in our article in the Journal of the American Chemical Society, 65, 1276 (1943), particularly at pages 1280 and 1281. under the subtitle 1-bromo-4,8,i2- trlmethyltridecane."

The 4,8,i2-trimethyl-tridecyi magnesium halide is preierably the bromide or chloride. The corresponding iodide may be used but the reaction is less eflicient. The 4,8,12-trimethyl-trldecyi masnesium halide is then reacted with acetaldehyde and the resultant Grignard addition product is hydrolysed under acidic conditions to form the carbine! which is then oxidized, so as to term the desired 6,i0,l4-trimethyl-pentadeem-2. The process is believed to be accuto Resents oi the Unirately represented by the following equations. which, however. should not be considered as a limitation-upon the invention:

I (CHOICHOHIOHsOHICHOHiCHsOHgCH CHsCHaCHMIX Hi H:

(4,8,l2-trimethyl-tridecyl mauissium halide. I being halogen) Ii CHsOH =0 (scstaldehyde) III 1 (CHihOHCHiCHlCH:OHOHiOHrOHICHOKsOHsCHgOHOM X Ha Ha Ha (Grignsrd addition product) drolysed mas m um W l (by scidicconditlon s) (cBl)lcHOHIOHICHIOHCHIOBlCHlOHOHI HIOHIOHOH Es He He (GJUJI-Mmethyl-pentadmol-fi) l (oxidised) V (CHs)rUHOHIOHsOHIOHOHIOHIOKsUHOHICHlQHIU O Ha Ha HI 6,10,14-trlmsthyl-pen It may be pointed out that the hydrolysis of Compound III may be carried out under alkaline, neutral, or acidic conditions, but as the magnesium is removed at this stage in the form of the hydroxide. the separation may be made most conveniently under slightly acid conditions or in the presence oi some reagent such as ammonium chloride solution in which the masnesium hy- 0 droxide is soluble. Under neutral or alkaline eondltions the magnesium hydroxide precipitates as a thick gel and can be removed only with dimculty.

The oxidation of Compound IV may be accomplished by any suitable oxidizing agent for converting alcohols to the corresponding carbonyl compounds. There are very many oxidizing agents of which a few, viz., sodium dichromate, potassium permanganate, and manganese dioxlde are exemplary. Sodium dichromate under acidic conditions (viz., acidified with sulfuric acid) is preferred because of low cost, favorable reaction conditions and availability.

The magnesium halide, Compound I, may be either the bromide, chloride or iodide, of which the bromide is preferred because of favorable yields. The chloride and iodide are also satisfactory, though less easily obtainable.

The invention is illustrated by the following example which, however, must not be considered as a limitation upon the invention.

Example A Grignard solution was prepared from 41.0 grams (0.135 mole) of pure 1-bromo-4,8,12-trimethyl-tridecane, (nD25=1.4598), Structure I, and 4.85 grams (0.2 mole) of magnesium in 75 cc. of dry ethyl ether. To the stirred solution which had been cooled to 0., there was slowly added 20 cc. of acetaldehyde, Structure II, in 50 cc. of dry ethyl ether. The reaction was completed by refluxing the mixture for $5 hour and resulted in the iormation oi the addition product, Structure III.

The Grlgnard addition product, Structure III, was extracted with more other, the combined ethereal solutions were washed with water, dried over sodium sulfate and the solvent was removed. The resultant alcohol, 6,10,14-trimethyl-penta decanol-Z was distilled and it boiled at 150-155" C./3 mm. Hg pressure, and was obtained in a yield oi 25.5 grams (70%). It had a refractive index or nD25=1Aa48 and contained 80.39% carbon and 13.88% hydrogen, whereas theoretical percentages of these constituents, calculated for CmHsaO are 79.91% carbon and 14.17% hydrogen Twenty-five grams (0.0025 mole) of the above 6,10,l4-trimethyl-pentadecanol-2, Structure IV, was dissolved in 30 cc. of benzene and slowly added to a well stirred solution of 21 grams (0.07 mole) of sodium dichromate in 8 cc. (0.14 mole) or concentrated sulfuric acid (density 1.84), 30 cc. of glacial acetic acid and 65 cc. of water. The temperature rose to 50' C.

and after it had fallen to 40 C., the stirred reaction mixture was maintained at the latter temperature for 1 hour. The orange-green mixture was extracted with ether, the ethereal layer separated and washed withwater and 5% sodium hydroxide and finally dried over sodium sulfate. The solvent was then removed' The residual 6,10,14 trimethyl pentadecanone-2 (Structure V), so prepared, boiled at ISO-152 C./3 mm. o! Hg pressure and weighed 18.7 grams (75.5%) yield. It had a refractive index of 11025: 1.4433 and contained 80.75% carbon and 13.30% hydrogen, whereas theoretical percentages of these ingredients calculated for 018K380 are 80.50% carbon and 13.53% hydrogen. The semi-carbazone oi 6,10,14-trimethylpentadecanone melted at -70.5 C.

It is noted that the name phytol-ketone" has sometimes been used to designate the compound 6,10,14-trimethyl-pentadecanone-2, because the compound was originally obtained by the oxidation of phytol. The name of this product, according to Geneva nomenclature is 6,10,14-trimethyl-pentadecanone-2. It has also been designated 2,6,10 trimethyl pentadecanone-l4 where the numbering is begun at the opposite end oi the molecule.

Many variations of the foregoing methods will be apparent to those skilled in the art, and are intended to be within the purview of the invention illustrated, described and claimed.

What we claim is:

l. The method of preparing 6,10,14-trimethylpentadecanone-2 which comprises reacting a 4,8,12-trimethyl-tridecyl magnesium halide and acetaldehyde, hydrolyzing the addition product so formed, oxidizing the resultant carbinol and separating the 6,10,14 trimethyl pentadecanone-2 so produced. 1

2. The method of preparing 6,10,14-trimethylpentadecanone-Z which comprises reacting 4.8,- lz-trimethyl-tridecyl magnesium bromide and acetaldehyde, hydrolyzing the addition product so Iormed, oxidizing the resultant carbinol, and separating the 6,10,14 trimethyl pentadecanone-2 so produced.

3. The method of preparing 6,10,14-trlmethylpentadecanone-2 which comprises reacting 4,8,- IZ-trimethyl-trldecyl magnesium chloride and acetaldehyde, hydrolyzing the addition product so formed, oxidizing the resultant carbinol and separating the 6,10,14 trimethyl pentadecanone-2 so produced.

LEE IRVIN SMITH. JOSEPH A. SPRUNG.

CERTIFICATE OF CORRECTION.

Patent No. 2,565,092.

November 21, 9%-

IEE IRVIN SMITH, ET AL.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction as follows:

line '26 and l and second column, line 12,

column,

Page 2, first for 'nD25 road 3"; and that the said Letters Patent should be read with this correction therein that the same may conform tothe record of the case the Patent Office.

Signed and sealed this 10th day of April, A. n. 19ll5.

(Seal) Leslie Frazer oting Ccsnmissioner of Patents.

dltions the magnesium hydroxide precipitates as a thick gel and can be removed only with dimculty.

The oxidation of Compound IV may be accomplished by any suitable oxidizing agent for converting alcohols to the corresponding carbonyl compounds. There are very many oxidizing agents of which a few, viz., sodium dichromate, potassium permanganate, and manganese dioxlde are exemplary. Sodium dichromate under acidic conditions (viz., acidified with sulfuric acid) is preferred because of low cost, favorable reaction conditions and availability.

The magnesium halide, Compound I, may be either the bromide, chloride or iodide, of which the bromide is preferred because of favorable yields. The chloride and iodide are also satisfactory, though less easily obtainable.

The invention is illustrated by the following example which, however, must not be considered as a limitation upon the invention.

Example A Grignard solution was prepared from 41.0 grams (0.135 mole) of pure 1-bromo-4,8,12-trimethyl-tridecane, (nD25=1.4598), Structure I, and 4.85 grams (0.2 mole) of magnesium in 75 cc. of dry ethyl ether. To the stirred solution which had been cooled to 0., there was slowly added 20 cc. of acetaldehyde, Structure II, in 50 cc. of dry ethyl ether. The reaction was completed by refluxing the mixture for $5 hour and resulted in the iormation oi the addition product, Structure III.

The Grlgnard addition product, Structure III, was extracted with more other, the combined ethereal solutions were washed with water, dried over sodium sulfate and the solvent was removed. The resultant alcohol, 6,10,14-trimethyl-penta decanol-Z was distilled and it boiled at 150-155" C./3 mm. Hg pressure, and was obtained in a yield oi 25.5 grams (70%). It had a refractive index or nD25=1Aa48 and contained 80.39% carbon and 13.88% hydrogen, whereas theoretical percentages of these constituents, calculated for CmHsaO are 79.91% carbon and 14.17% hydrogen Twenty-five grams (0.0025 mole) of the above 6,10,l4-trimethyl-pentadecanol-2, Structure IV, was dissolved in 30 cc. of benzene and slowly added to a well stirred solution of 21 grams (0.07 mole) of sodium dichromate in 8 cc. (0.14 mole) or concentrated sulfuric acid (density 1.84), 30 cc. of glacial acetic acid and 65 cc. of water. The temperature rose to 50' C.

and after it had fallen to 40 C., the stirred reaction mixture was maintained at the latter temperature for 1 hour. The orange-green mixture was extracted with ether, the ethereal layer separated and washed withwater and 5% sodium hydroxide and finally dried over sodium sulfate. The solvent was then removed' The residual 6,10,14 trimethyl pentadecanone-2 (Structure V), so prepared, boiled at ISO-152 C./3 mm. o! Hg pressure and weighed 18.7 grams (75.5%) yield. It had a refractive index of 11025: 1.4433 and contained 80.75% carbon and 13.30% hydrogen, whereas theoretical percentages of these ingredients calculated for 018K380 are 80.50% carbon and 13.53% hydrogen. The semi-carbazone oi 6,10,14-trimethylpentadecanone melted at -70.5 C.

It is noted that the name phytol-ketone" has sometimes been used to designate the compound 6,10,14-trimethyl-pentadecanone-2, because the compound was originally obtained by the oxidation of phytol. The name of this product, according to Geneva nomenclature is 6,10,14-trimethyl-pentadecanone-2. It has also been designated 2,6,10 trimethyl pentadecanone-l4 where the numbering is begun at the opposite end oi the molecule.

Many variations of the foregoing methods will be apparent to those skilled in the art, and are intended to be within the purview of the invention illustrated, described and claimed.

What we claim is:

l. The method of preparing 6,10,14-trimethylpentadecanone-2 which comprises reacting a 4,8,12-trimethyl-tridecyl magnesium halide and acetaldehyde, hydrolyzing the addition product so formed, oxidizing the resultant carbinol and separating the 6,10,14 trimethyl pentadecanone-2 so produced. 1

2. The method of preparing 6,10,14-trimethylpentadecanone-Z which comprises reacting 4.8,- lz-trimethyl-tridecyl magnesium bromide and acetaldehyde, hydrolyzing the addition product so Iormed, oxidizing the resultant carbinol, and separating the 6,10,14 trimethyl pentadecanone-2 so produced.

3. The method of preparing 6,10,14-trlmethylpentadecanone-2 which comprises reacting 4,8,- IZ-trimethyl-trldecyl magnesium chloride and acetaldehyde, hydrolyzing the addition product so formed, oxidizing the resultant carbinol and separating the 6,10,14 trimethyl pentadecanone-2 so produced.

LEE IRVIN SMITH. JOSEPH A. SPRUNG.

CERTIFICATE OF CORRECTION.

Patent No. 2,565,092.

November 21, 9%-

IEE IRVIN SMITH, ET AL.

It is hereby certified that error appears in the printed specification of the above numbered patent requiring correction as follows:

line '26 and l and second column, line 12,

column,

Page 2, first for 'nD25 road 3"; and that the said Letters Patent should be read with this correction therein that the same may conform tothe record of the case the Patent Office.

Signed and sealed this 10th day of April, A. n. 19ll5.

(Seal) Leslie Frazer oting Ccsnmissioner of Patents. 

